Coinheritance of generalized pustular psoriasis and familial Behçet-like autoinflammatory syndrome with variants in IL36RN and TNFAIP3 in the heterozygous state

J Dermatol. 2019 Oct;46(10):907-910. doi: 10.1111/1346-8138.15034. Epub 2019 Jul 29.

Abstract

Generalized pustular psoriasis (GPP) is now known to be caused by biallelic variants in IL36RN and monoallelic variants in CARD14 and AP1S3. The presence of a modifier locus or oligogenic inheritance have been hypothesized. We report on a patient with a unique coinheritance of pathogenic variants in IL36RN (c.115+6T>C) and TNFAIP3 (c.547C>T, p.R183*) causing the genetic entities GPP and familial Behçet-like autoinflammatory syndrome (AISBL). The heterozygous variant in IL36RN identified by Sanger sequencing was inherited from his unaffected father, while the heterozygous variant in TNFAIP3 was detected by whole-exome sequencing and was also identified in the patient's AISBL-affected maternal relatives. Further functional studies are required to research whether the variant of TNFAIP3 plays a part in the development of GPP or simply causes the Behçet's disease phenotype. However, our data suggest that whole-exome sequencing for the heterozygous carrier of the IL36RN gene in GPP be used to find the potential second genetic locus.

Keywords: IL36RN; TNFAIP3; coinheritance; familial Behçet-like autoinflammatory syndrome; generalized pustular psoriasis.

Publication types

  • Case Reports

MeSH terms

  • Asian People
  • Behcet Syndrome / diagnosis
  • Behcet Syndrome / genetics*
  • Child, Preschool
  • Genetic Predisposition to Disease
  • Heterozygote
  • Humans
  • Interleukins / genetics*
  • Male
  • Multifactorial Inheritance
  • Mutation
  • Pedigree
  • Psoriasis / diagnosis
  • Psoriasis / genetics*
  • Tumor Necrosis Factor alpha-Induced Protein 3 / genetics*

Substances

  • IL36RN protein, human
  • Interleukins
  • TNFAIP3 protein, human
  • Tumor Necrosis Factor alpha-Induced Protein 3